1. Academic Validation
  2. Role of TREM-1 in the development of early brain injury after subarachnoid hemorrhage

Role of TREM-1 in the development of early brain injury after subarachnoid hemorrhage

  • Exp Neurol. 2021 Jul;341:113692. doi: 10.1016/j.expneurol.2021.113692.
Xin-Gang Sun 1 Mi-Mi Zhang 2 Shao-Yu Liu 2 Xue-Hong Chu 2 Guo-Qiang Xue 3 Bao-Chen Zhang 3 Jia-Bao Zhu 3 Ivan Steve Godje Godje 2 Li-Juan Zhu 2 Hui-Yu Hu 2 Hai-Wang 2 Ying-Jie Shen 2 Gai-Qing Wang 4
Affiliations

Affiliations

  • 1 Department of Neurology, the Second Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030000, People's Republic of China. Electronic address: sunyanxia820701@163.com.
  • 2 Shanxi Medical University, Taiyuan, Shanxi 030000, People's Republic of China.
  • 3 Department of Neurosurgery, Yuncheng Hospital Affiliated to Shanxi Medical University, Yuncheng, Shanxi 044000, People's Republic of China.
  • 4 Department of Neurology, the Second Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030000, People's Republic of China.
Abstract

Triggering receptor expressed on myeloid cells-1 (TREM-1) was found to be induced in the context of subarachnoid hemorrhage (SAH) before. This study further investigates its role in the development of SAH-induced early brain injury (EBI). Firstly, rats were randomly divided into Sham and SAH groups for analysis of temporal patterns and cellular localization of TREM-1. Secondly, TREM-1 intervention was administrated to produce Sham, vehicle, antagonist and agonist groups, for analyzing TREM-1, Toll-like Receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and NF-κB expressions at 24 h post-modeling, and EBI assessment at 24 h and 72 h. Thirdly, TLR4 Inhibitor (TAK-242) was exploited to produce Sham, Sham+TAK-242, SAH, and SAH + TAK-242 groups to analyze the effects of TLR4 inhibition on TREM-1 induction and EBI evaluation at 72 h. Fourthly, the relationship of soluble TREM-1 (sTREM-1) levels in cerebrospinal fluid of SAH patients with Hunt-Hess grades were explored. The results showed that TREM-1 increased in the brain after experimental SAH (eSAH) early at 6 h and peaked at 48 h, which was found to be located in microglia and endothelial cells. TREM-1 inhibition attenuated EBI associated with TLR4/MyD88/NF-κB suppression, while enhancement had the opposite effects. Contrarily, TLR4 inhibition prevented TREM-1 induction and ameliorated EBI. In addition, sTREM-1 levels in SAH patients positively correlated with Hunt-Hess grades. Overall, the present study provides new evidence that TREM-1 increases dynamically in the brain after eSAH and it is located in microglia and endothelial cells, which may aggravate EBI by interacting with TLR4 pathway. And sTREM-1 in patients might act as a monitoring biomarker of EBI, providing new insights for future studies.

Keywords

Early brain injury; MyD88; NF-κB; Subarachnoid hemorrhage; TLR4; TREM-1.

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